Serotonergic neurotransmission may be involved in the etiology of schizophrenia. We systematically searched for human tryptophan hydroxylase (TPH) coding polymorphisms, and detected a novel pentanucleotide repeat deletion polymorphism (GTTTT)4/5 in TPH intron 1b. We also confirmed A779C intron 7. Neither polymorphism showed a significant association with schizophrenia (182 patients with schizophrenia, 148 controls). A significant association, however, between A779C genotypes and the total Manchester Scale (MS) scores was found in male patients (P = 0.045). Subsequently, a significant association was also found between A779C genotypes and the MS negative symptoms scores in male patients (P = 0.030). These results suggest that the TPH gene may play a role in the negative symptoms in male patients with schizophrenia.